This application addresses the broad Challenge Area (05) Comparative Effectiveness Research and the specific Challenge Topic: 05-NS-104* Intervention vs. Best Medical Therapy in Asymptomatic Persons With Identified Vascular Abnormalities. The International Study of Unruptured Intracranial Aneurysms (ISUIA) study group undertook an initial epidemiological project on September 1, 1991, to determine the natural history of unruptured intracranial aneurysms (UIAs) and the morbidity and mortality associated with repair of these lesions to help define the optimal management of patients with UIAs. Over the past 17 years, 5,500 patients at 61 medical centers were entered and followed as called for in the study protocol. The hypotheses and specific aims for ISUIA were to determine the long-term risk of hemorrhage, risk factors for hemorrhage, the long-term disability rates and factors related to disability, and risk of death. The average follow-up of the prospective cohort was 8.6 years with a total of 34,800 person-years. The proposed continuation of secondary analysis will address key questions that became evident through the conduct and results of Phase III of ISUIA. Aim 1: In addition to size and location, aneurysm shape and morphology may be predictive of hemorrhage and adverse outcome of surgery or endovascular treatment. We propose to analyze the existing ISUIA data to determine the shape of intracranial aneurysms and impact on occurrence of hemorrhage and treatment outcome. We will validate the variation in shape through direct digitization of the angiograms. We will determine the role of size, morphology and shape in predicting aneurismal hemorrhage. We will determine the role of size, morphology and shape in surgical and endovascular morbidity and mortality. Aim 2: Analysis of the long-term outcome of patients in ISUIA showed that aneurismal hemorrhage accounted for 10% of deaths. This aim will determine risk factors for overall morbidity and mortality. In order to accomplish this aim we will conduct competing risk analysis of mortality, determine risk factors for aneurismal and non-aneurismal outcomes, and will compare overall outcome of the retrospective and prospective cohorts. Aim 3: ISUIA included a prospective non-randomized cohort of 4059 patients. The analysis based upon the aims of the prior grants to date has been within the unoperated, surgical and endovascular subgroups. We propose to compare long-term hemorrhage and outcome by treatment resulting in a decision analysis. First we will perform an analysis of the prospective cohort of the decision for treatment. Second, using propensity score adjustment, we will compare the long-term risk of hemorrhage and outcome between treatment groups. Third, we will utilize the comparisons and subgroups to perform a decision analysis. This meets the aims of the Challenge Grant topic 05-NS-104: Intervention vs. Best Medical Therapy in Asymptomatic Persons With Identified Vascular Abnormalities by identifying patients who are at risk of aneurismal hemorrhage by examining shape and morphology of the aneurysm, by identifying patients who are at risk of hemorrhage versus other causes of morbidity and mortality to increase the efficiency of clinical trials, and to use data from ISUIA to assess the long-term effectiveness in comparable patients, estimating short-term and long-term results to identify appropriate risk strata for ongoing study and for clinical trials. The proposed analysis of the ISUIA cohort will further define the risk of aneurysm rupture, the competing causes of death and the effectiveness of hemorrhage prevention through surgical and endovascular treatment.